A simple and reproducible model of spinal cord injury induced by epidural balloon inflation in the rat.

This paper describes a modification of a balloon-compression technique to produce spinal cord injury in adult rats. A 2-French Fogarty catheter is inserted into the dorsal epidural space through a small hole made in T10 vertebral arch, advanced cranially to T8-9 spinal level, and inflated for 5 min. Spinal cord damage is graded by increasing the volume of saline used to inflate the balloon. Quantitative neurological and histopathological outcomes are presented with three different volumes (10, 15, and 20 microl of saline) to characterize the gradation of injury. Volume of 15 microl produced complete paraplegia followed by gradual recovery, finally reaching approximately the middle of the scale used to quantitate the locomotor performance. With these animals, after 4 weeks, the center of the lesion shows complete loss of grey matter and partial sparing of the white matter. We conclude that 15 microl volume produced submaximal injury that will be useful for studying the pathophysiology and effects of protective therapies with this compression-injury model.

Intrathecal administration of dizocilpine maleate (MK-801) attenuates ischemic damage in the rabbit spinal cord.

The therapeutic efficacy of intrathecally administered MK-801 (dizocilpine maleate), a noncompetitive receptor antagonist of N-methyl-D-aspartate receptor complex, was investigated in a rabbit spinal cord ischemia model. Normal saline, 0.3 ml (control, n = 4) or MK-801, 150 micrograms in 0.3 ml of saline, was administered intrathecally at the level of the lumbar enlargement, 30 min before (pretreatment, n = 7) or in the first min after (post-treatment, n = 4) 30 min of aortic occlusion followed by 2-h reperfusion. Nauta silver method was used for histopathological evaluation of lumbosacral segments. The degree of gray matter damage (argyrophilic neurons) was evaluated in three areas: A1, Rexed's laminae I-VI; A2, laminae VII and X; and A3, laminae VIII-IX. Pre- and post-treatment with MK-801 decreased the number of argyrophilic neurons (P < 0.05) in all areas examined. The number of argyrophilic neurons in A1, A2, and A3 was reduced by 59, 28, and 29%, respectively, by MK-801 pretreatment and by 87, 66, and 46%, respectively, by MK-801 post-treatment. Our results show that with single bolus intrathecal administration the efficacy of MK-801 was greater with post- compared to pretreatment and most dramatic in Rexed's laminae I-VI compared to laminae VII-X. Intrathecal administration of MK-801 prior to or at the beginning of the recirculation diminishes the extent of postischemic neuronal spinal cord damage at early postreperfusion period.

Free and peptide-bound amino acids as indicators of ischemic damage of the rabbit spinal cord.

The concentrations of free and peptide-bound amino acids aspartate (Asp), glutamate (Glu), glycine (Gly) and gamma-aminobutyric acid (GABA) were studied following ischemia and recirculation in the ventral and dorsal gray matter of the rabbit spinal cord. No changes in the concentration of amino acids following ten minutes (min) of ischemia and four days of recovery were found. The most significant change after 20 min, and especially 40 min, of ischemia was a decrease in free Asp and GABA levels in both parts of the gray matter. The relatively greater decrease in the concentration of free amino acids in the ventral horns corresponds with the greater morphological damage to this part of spinal cord following ischemia. Following 40 min of ischemia and recirculation decrease in peptide-bound Glu in the ventral horns and Asp and Glu in the dorsal horns was found.